Trafficking of the major virulence factor to the surface of transfected P falciparum-infected erythrocytes
Trafficking of the major virulence factor to the surface of transfected P falciparum-infected erythrocytes
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DOI：
10.1182/blood-2004-12-4666
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发表时间：
2005-05-15
期刊：
影响因子：
20.3
通讯作者：
Cowman, AF
中科院分区：
文献类型：
--
作者：
Knuepfer, E;Rug, M;Cowman, AF
在入侵人类红细胞（红细胞）后，疟疾寄生虫恶性疟原虫通过将蛋白质运输到红细胞隔室来重塑宿主细胞。毒力蛋白恶性疟原虫红细胞膜蛋白1 （PfEMP1）负责感染细胞粘附宿主内皮受体。该蛋白通过寄生虫的质膜和寄生液泡膜输出并插入红细胞膜。我们利用绿色荧光蛋白嵌合体和荧光光漂白实验跟踪PfEMP1通过感染红细胞的输出。我们的数据显示，附着在PfEMP1跨膜结构域和c端结构域上的一个旋钮相关的富组氨酸蛋白（KAHRP） n端蛋白输出元件足以有效地将蛋白结构域运输到感染恶性疟原虫的红细胞外部。输出蛋白的物理状态表明以复合物形式而不是以囊泡形式进行运输，这支持了内源性PfEMP1以类似方式运输的假设。本研究确定了在恶性疟原虫感染的红细胞膜外表达蛋白所需的序列。(c) 2005年由美国血液学会出版。
After invading human red blood cells (RBCs) the malaria parasite Plasmodium falciparum remodels the host cell by trafficking proteins to the RBC compartment. The virulence protein P falciparum erythrocyte membrane protein 1 (PfEMP1) is responsible for cytoadherence of infected cells to host endothelial receptors. This protein is exported across the parasite plasma membrane and parasitophorous vacuole membrane and inserted into the RBC membrane. We have used green fluorescent protein chimeras and fluorescence photobleaching experiments to follow PfEMP1 export through the infected RBC. Our data show that a knob-associated histidine-rich protein (KAHRP) N-terminal protein export element appended to the PfEMP1 transmembrane and C-terminal domains was sufficient for efficient trafficking of protein domains to the outside of the P falciparum-in-infected RBC. The physical state of the exported proteins suggests trafficking as a complex rather than in vesicles and supports the hypothesis that endogenous PfEMP1 is trafficked in a similar manner. This study identifies the sequences required for expression of proteins to the outside of the P falciparurn-infected RBC membrane. (c) 2005 by The American Society of Hematology.